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Membranes
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Function and Malfunction of Ion Channels in Biological Cell Membrane
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Function and Malfunction of Ion Channels in Biological Cell Membrane

A special issue of Membranes (ISSN 2077-0375). This special issue belongs to the section "Biological Membrane Functions".

Deadline for manuscript submissions: closed (20 December 2023) | Viewed by 9866

Special Issue Editor

Dr. Masaki Morishima

E-Mail Website
Guest Editor
Department of Food Science and Nutrition, Faculty of Agriculture, Kindai University, 3327-204 Nakamachi, Nara 631-8505, Japan
Interests: ion channel; transporters; receptor; electrophysiology; arrhythmia; oxidative stress; cellular signals; protein kinases; membrane potentials

Special Issue Information

Dear Colleagues,

Ion channels are usually composed of several aggregated subunit proteins which form dynamic pores in the cellular membrane allowing for passage through the ions across the impermeant lipid cell membrane. The flows of calcium, potassium, and sodium ions are very important in many cellular processes, such as muscle contractions in the heart, pancreatic insulin release, the transmission of impulses in the nervous system such as excitation, and T cell activation. Multiple functions of ion channels, which, besides their well-recognized role in controlling cell excitability and ionic and fluid control, have been emerged as particularly relevant in several pathological conditions and diseases concerning the cardiovascular, kidney, skeletal muscle, and brain/nervous systems. For instance, cardiac ion channels are critical for all aspects of cardiac function, including rhythmicity and contractility. Vice versa, ion channel malfunctions are critical in several aspects of cardiac arrhythmias and heart failure. Consequently, ion channels could be key targets for therapeutic intervention in many organ diseases, including those of the heart. Recently, it has been widely recognized that ion channels contribute to the growth of tumours/cancers, suggesting that ion channels are potential pharmacological targets for tumour therapy. This Special Issue focuses on recent research that elucidates cellular and molecular mechanisms for ion channel regulation and dysregulation, and discusses novel implications for membrane proteins, trafficking, and cellular signalling, with particular attention paid to molecular, cellular, organ, and physical dysfunctions. In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: biomedical research, applied biology, physiology, pharmacology, and medical proteomics.

We look forward to receiving your contributions.

Dr. Masaki Morishima
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Membranes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • ion channels
  • electrical remodelling
  • fluid homeostasis
  • transcriptional regulation
  • membrane potentials
  • intracellular signal molecules
  • excitation

Published Papers (6 papers)

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Research

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11 pages, 1735 KiB  
Article
Brownian Aging as One of the Mechanistic Components That Shape the Single-Channel Ionic Currents through Biological and Synthetic Membranes
by Agata Wawrzkiewicz-Jałowiecka and Andrzej Fuliński
Membranes 2023, 13(11), 879; https://doi.org/10.3390/membranes13110879 - 11 Nov 2023
Viewed by 1160
Abstract
Semipermeable membranes enable the separation of a given system from its environment. In biological terms, they are responsible for cells’ identity. In turn, the functioning of ion channels is crucial for the control of ionic fluxes across the membranes and, consequently, for the [...] Read more.
Semipermeable membranes enable the separation of a given system from its environment. In biological terms, they are responsible for cells’ identity. In turn, the functioning of ion channels is crucial for the control of ionic fluxes across the membranes and, consequently, for the exchange of chemical and electrical signals. This paper presents a model and simulations of currents through ionic nanochannels in an attempt to better understand the physical mechanism(s) of open/closed (O/C) sequences, i.e., random interruptions of ionic flows through channels observed in all known biochannels and in some synthetic nanopores. We investigate whether aging, i.e., the changes in Brownian motion characteristics with the lapse of time, may be at least one of the sources of the O/C sequences (in addition to the gating machinery in biochannels). The simulations based on the approximated nanostructure of ion channels confirm this postulation. The results also show the possibility of changing the O/C characteristics through an appropriate alteration of the channel surroundings. This observation may be valuable in technical uses of nanochannels in synthetic membranes and allow for a better understanding of the reason for the differences between the biochannels’ activity in diverse biological membranes. Proposals of experimental verification of this aging O/C hypothesis are also presented. Full article
(This article belongs to the Special Issue Function and Malfunction of Ion Channels in Biological Cell Membrane)
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22 pages, 6995 KiB  
Article
Molecular Cloning, Expression and Transport Activity of SaNPF6.3/SaNRT1.1, a Novel Protein of the Low-Affinity Nitrate Transporter Family from the Euhalophyte Suaeda altissima (L.) Pall.
by Olga I. Nedelyaeva, Dmitrii E. Khramov, Lyudmila A. Khalilova, Alena O. Konoshenkova, Anastasia V. Ryabova, Larissa G. Popova, Vadim S. Volkov and Yurii V. Balnokin
Membranes 2023, 13(10), 845; https://doi.org/10.3390/membranes13100845 - 22 Oct 2023
Viewed by 1829
Abstract
The SaNPF6.3 gene, a putative ortholog of the dual-affinity nitrate (NO3−) transporter gene AtNPF6.3/AtNRT1.1 from Arabidopsis thaliana, was cloned from the euhalophyte Suaeda altissima. The nitrate transporting activity of SaNPF6.3 was studied by heterologous expression of [...] Read more.
The SaNPF6.3 gene, a putative ortholog of the dual-affinity nitrate (NO3−) transporter gene AtNPF6.3/AtNRT1.1 from Arabidopsis thaliana, was cloned from the euhalophyte Suaeda altissima. The nitrate transporting activity of SaNPF6.3 was studied by heterologous expression of the gene in the yeast Hansenula (Ogataea) polymorpha mutant strain Δynt1 lacking the original nitrate transporter. Expression of SaNPF6.3 in Δynt1 cells rescued their ability to grow on the selective medium in the presence of nitrate and absorb nitrate from this medium. Confocal laser microscopy of the yeast cells expressing the fused protein GFP-SaNPF6.3 revealed GFP (green fluorescent protein) fluorescence localized predominantly in the cytoplasm and/or vacuoles. Apparently, in the heterologous expression system used, only a relatively small fraction of the GFP-SaNPF6.3 reached the plasma membrane of yeast cells. In S. altissima plants grown in media with either low (0.5 mM) or high (15 mM) NO3−; concentrations, SaNPF6.3 was expressed at various ontogenetic stages in different organs, with the highest expression levels in roots, pointing to an important role of SaNPF6.3 in nitrate uptake. SaNPF6.3 expression was induced in roots of nitrate-deprived plants in response to raising the nitrate concentration in the medium and was suppressed when the plants were transferred from sufficient nitrate to the lower concentration. When NaCl concentration in the nutrient solution was elevated, the SaNPF6.3 transcript abundance in the roots increased at the low nitrate concentration and decreased at the high one. We also determined nitrate and chloride concentrations in the xylem sap excreted by detached S. altissima roots as a function of their concentrations in the root medium. Based on a linear increase in Cl− concentrations in the xylem exudate as the external Cl− concentration increased and the results of SaNPF6.3 expression experiments, we hypothesize that SaNPF6.3 is involved in chloride transport along with nitrate transport in S. altissima plants. Full article
(This article belongs to the Special Issue Function and Malfunction of Ion Channels in Biological Cell Membrane)
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13 pages, 2824 KiB  
Article
Effect of Fusidic Acid and Some Nitrogen-Containing Derivatives on Liposomal and Mitochondrial Membranes
by Mikhail V. Dubinin, Anna I. Ilzorkina, Elena V. Salimova, Manish S. Landage, Ekaterina I. Khoroshavina, Sergey V. Gudkov, Konstantin N. Belosludtsev and Lyudmila V. Parfenova
Membranes 2023, 13(10), 835; https://doi.org/10.3390/membranes13100835 - 20 Oct 2023
Viewed by 1334
Abstract
The paper assesses the membranotropic action of the natural antibiotic fusidic acid (FA) and its derivatives. It was found that a FA analogue with ethylenediamine moiety (derivative 2), in contrast to native FA and 3,11-dioxime analogue (derivative 1), is able to increase the [...] Read more.
The paper assesses the membranotropic action of the natural antibiotic fusidic acid (FA) and its derivatives. It was found that a FA analogue with ethylenediamine moiety (derivative 2), in contrast to native FA and 3,11-dioxime analogue (derivative 1), is able to increase the mobility of the lipid bilayer in the zone of lipid headgroups, as well as to induce permeabilization of lecithin liposome membranes. A similar effect of derivative 2 is also observed in the case of rat liver mitochondrial membranes. We noted a decrease in the microviscosity of the mitochondrial membrane and nonspecific permeabilization of organelle membranes in the presence of this agent, which was accompanied by a decrease in mitochondrial Δψ and OXPHOS efficiency. This led to a reduction in mitochondrial calcium retention capacity. The derivatives also reduced the production of H2O2 by mitochondria. The paper considers the relationship between the structure of the tested compounds and the observed effects. Full article
(This article belongs to the Special Issue Function and Malfunction of Ion Channels in Biological Cell Membrane)
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12 pages, 5613 KiB  
Article
The Interplay between TRPM7 and MagT1 in Maintaining Endothelial Magnesium Homeostasis
by Sara Castiglioni, Laura Locatelli, Giorgia Fedele, Alessandra Cazzaniga, Emil Malucelli, Stefano Iotti and Jeanette A. Maier
Membranes 2023, 13(3), 286; https://doi.org/10.3390/membranes13030286 - 28 Feb 2023
Cited by 1 | Viewed by 1455
Abstract
The transient receptor potential cation channel subfamily M member 7 (TRPM7) is an ubiquitous channel fused to an α-kinase domain involved in magnesium (Mg) transport, and its level of expression has been proposed as a marker of endothelial function. To broaden our present [...] Read more.
The transient receptor potential cation channel subfamily M member 7 (TRPM7) is an ubiquitous channel fused to an α-kinase domain involved in magnesium (Mg) transport, and its level of expression has been proposed as a marker of endothelial function. To broaden our present knowledge about the role of TRPM7 in endothelial cells, we generated stable transfected Human Endothelial Cells derived from the Umbilical Vein (HUVEC). TRPM7-silencing HUVEC maintain the actin fibers’ organization and mitochondrial network. They produce reduced amounts of reactive oxygen species and grow faster than controls. Intracellular Mg concentration does not change in TRPM7-silencing or -expressing HUVEC, while some differences emerged when we analyzed intracellular Mg distribution. While the levels of the plasma membrane Mg transporter Solute Carrier family 41 member 1 (SLC41A1) and the mitochondrial channel Mrs2 remain unchanged, the highly selective Magnesium Transporter 1 (MagT1) is upregulated in TRPM7-silencing HUVEC through transcriptional regulation. We propose that the increased amounts of MagT1 grant the maintenance of intracellular Mg concentrations when TRPM7 is not expressed in endothelial cells. Full article
(This article belongs to the Special Issue Function and Malfunction of Ion Channels in Biological Cell Membrane)
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22 pages, 1495 KiB  
Review
Water, Protons, and the Gating of Voltage-Gated Potassium Channels
by Alisher M. Kariev and Michael E. Green
Membranes 2024, 14(2), 37; https://doi.org/10.3390/membranes14020037 - 29 Jan 2024
Viewed by 1740
Abstract
Ion channels are ubiquitous throughout all forms of life. Potassium channels are even found in viruses. Every cell must communicate with its surroundings, so all cells have them, and excitable cells, in particular, especially nerve cells, depend on the behavior of these channels. [...] Read more.
Ion channels are ubiquitous throughout all forms of life. Potassium channels are even found in viruses. Every cell must communicate with its surroundings, so all cells have them, and excitable cells, in particular, especially nerve cells, depend on the behavior of these channels. Every channel must be open at the appropriate time, and only then, so that each channel opens in response to the stimulus that tells that channel to open. One set of channels, including those in nerve cells, responds to voltage. There is a standard model for the gating of these channels that has a section of the protein moving in response to the voltage. However, there is evidence that protons are moving, rather than protein. Water is critical as part of the gating process, although it is hard to see how this works in the standard model. Here, we review the extensive evidence of the importance of the role of water and protons in gating these channels. Our principal example, but by no means the only example, will be the Kv1.2 channel. Evidence comes from the effects of D2O, from mutations in the voltage sensing domain, as well as in the linker between that domain and the gate, and at the gate itself. There is additional evidence from computations, especially quantum calculations. Structural evidence comes from X-ray studies. The hydration of ions is critical in the transfer of ions in constricted spaces, such as the gate region and the pore of a channel; we will see how the structure of the hydrated ion fits with the structure of the channel. In addition, there is macroscopic evidence from osmotic experiments and streaming current measurements. The combined evidence is discussed in the context of a model that emphasizes the role of protons and water in gating these channels. Full article
(This article belongs to the Special Issue Function and Malfunction of Ion Channels in Biological Cell Membrane)
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13 pages, 1255 KiB  
Review
TRP Channels: The Neglected Culprits in Breast Cancer Chemotherapy Resistance?
by Mayar Soussi, Alice Hasselsweiller and Dimitra Gkika
Membranes 2023, 13(9), 788; https://doi.org/10.3390/membranes13090788 - 12 Sep 2023
Viewed by 1230
Abstract
Breast cancer is a major health concern worldwide, and resistance to therapies remains a significant challenge in treating this disease. In breast cancer, Transient Receptor Potential (TRP) channels are well studied and constitute key players in nearly all carcinogenesis hallmarks. Recently, they have [...] Read more.
Breast cancer is a major health concern worldwide, and resistance to therapies remains a significant challenge in treating this disease. In breast cancer, Transient Receptor Potential (TRP) channels are well studied and constitute key players in nearly all carcinogenesis hallmarks. Recently, they have also emerged as important actors in resistance to therapy by modulating the response to various pharmaceutical agents. Targeting TRP channels may represent a promising approach to overcome resistance to therapies in breast cancer patients. Full article
(This article belongs to the Special Issue Function and Malfunction of Ion Channels in Biological Cell Membrane)
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